P. Herlin

Metabolism of monoamines in the brain after total hepatectomy in the rat.

Rats were subjected to total hepatectomy or a sham operation and infused 5 h with 10% glucose solution. The metabolism of indoleamines and catecholamines was studied in five regions of the brain and two regions of the spinal cord by using a decarboxylase inhibitor (NSD 1015) blocking the conversion of 5-hydroxytryptophan (5-HTP) to serotonin and DOPA to dopamine. In the brain the concentrations of 5-HTP, serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) were elevated in all regions compared with controls except for serotonin in the mesencephalon-pons. In the spinal cord the concentrations of 5-HIAA were elevated whereas the concentrations of 5-HTP and serotonin were unchanged. The concentrations of DOPA were increased in the mesencephalon-pons whereas those of norepinephrine were decreased in cortex and mesencephalon-pons compared with controls. The results suggest an increased synthesis rate of the indoleamines in the brain and probably also of the catecholamines in the mesencephalon-pons at 5 h after hepatectomy.

A Microsurgical Method for Total Hepatectomy in the Rat

A microsurgical three-stage-procedure for total hepatectomy in the rat is described. In the first stage, suprarenal ligature and division of the inferior vena cava is performed. A modified portacaval shunt is constructed in the second stage and total hepatectomy is performed in the third stage. Microsurgical technique is of great benefit in both the second and third stages, especially in choosing the proper location for the shunt and minimizing blood loss. All the rats survived to the 6-hour study and 65% of the rats survived to the 18-hour study, despite the fact that body temperature was upheld to a level of 35-37 degrees C. Based on our experience in 165 hepatectomies, we recommend our method for metabolic studies in anhepatic rats.

MESOCAVAL SHUNT OR REPEATED SCLEROTHERAPY - EFFECTS ON REBLEEDING AND ENCEPHALOPATHY - A RANDOMIZED TRIAL

BACKGROUND Sclerotherapy is usually effective in controlling acutely bleeding esophageal varices. It may not be as effective as shunt surgery for prevention of rebleeding; therefore we undertook a prospective study comparing interposition mesocaval shunt (MCS) and repeated sclerotherapy. METHODS Forty-five patients (mean age, 52.6 +/- 9.8 years) with variceal bleeding were randomized after emergency endoscopic sclerotherapy either to repeat variceal obliteration followed by regular check endoscopy (n = 21) or to elective interposition mesocaval shunting by use of 14 mm polytetrafluoroethylene graft (n = 24). There was an equal distribution of Childs classes in the two groups. RESULTS In the sclerotherapy group 12 patients had recurrent hemorrhages causing five deaths compared with the shunt group, in which four patients had postoperative bleeding but without associated death. No difference was noted in the incidence of encephalopathy despite the development of total shunting 1 year after MCS. The median hospital stay was similar; 34.5 days (MCS) and 33 days (sclerotherapy). The number of intensive care unit days was also similar in the two groups. No difference was noted in survival in patients with Childs A and Childs B disease in the treatment groups. In patients with Childs C cirrhosis there was a statistically significant longer survival in patients undergoing MCS compared with patients undergoing sclerotherapy. CONCLUSIONS The results of the study show that the rate of rebleeding is significantly higher after sclerotherapy than after mesocaval shunting. In patients with Childs C cirrhosis MCS may be an alternative to sclerotherapy for the prevention of rebleeding from esophageal varices in patients not suitable for transplantation.

Infusion Tomography and Ultrasonography of the Gallbladder in the Diagnosis of Acute Cholecystitis

Sixty-three patients with the clinical suspicion of acute cholecystitis were examined with infusion tomography of the gallbladder. Ultrasonography was performed in 51 of these cases. The technique and diagnostic principles of both methods are discussed. The diagnostic value of the two methods when used in combination is stressed. Thus in a case of gangrenous cholecystitis when opacification of the gallbladder wall may not appear at infusion tomography, ultrasonography may demonstrate signs of gallbladder disease. Infusion tomography, on the other hand, may be of great value if ultrasonography is not informative.

Postoperative acute acalculous cholecystitis--an assessment of diagnostic procedures.

Two cases with postoperative acute acalculous cholecystitis diagnosed by computed tomography (CT) and ultrasonography are described. This rare postoperative complication is briefly reviewed. The mortality from this complication is high because the diagnosis is often missed. Use of diagnostic tools such as ultrasonography and CT increases the possibilities of reaching a correct diagnosis and therefore improves the prognosis.

The Effect of Ammonia Infusion on Brain Monoamine Metabolism in Portacaval-Shunted Rats*

SummaryThe effect of ammonia infusion on monoamine metabolism was studied in the rat brain. Seven days after portacaval shunt (PCS) or sham operation animals were infused with ammonia or saline. Brain metabolism of serotonin and norepinephrine was studied after injection of a decarboxylase inhibitor (m-hydroxybenzylhydrazine, NSD 1015) which blocks the conversion of 5-hydroxytryptophan to serotonin and dihydroxyphenylalanine to dopamine. Neurologic testing was conducted before killing. Plasma and brain amino acids were measured.PCS animals infused with ammonia were in deep coma after 6 h infusion, whereas sham-operated animals were virtually unaffected. Brain amino acid analyses demonstrated increased concentrations of the aromatic amino acids and a tenfold increase in glutamine. Serotonin metabolism was diminished after 6 h. Dopamine synthesis was normal, but norepinephrine levels were low after 6 h.The study suggests that hyperammonemia in PCS rats results in a depression of the serotonin synthesis rate in accordance with two previous studies but in contrast to previous hypotheses on the regulation of serotonin metabolism.

Serotonin receptors in the brain following total hepatectomy in rats treated with branched-chain amino acids

Serotonin concentrations and receptor binding characteristics were investigated in rats subjected to total hepatectomy, portacaval shunt (PCS) or sham-operation. The animals were infused for 5 hr with a 10% glucose solution or the same solution enriched with 0.24 M branched-chain amino acids (BCAA). Hepatectomized animals were in grade-two coma at the end of the experiment independent of infusion. Indoleamines in mesencephalon-pons and diencephalon were analyzed by high-pressure liquid chromatography with electrochemical detection. Serotonin receptors (5-HT1 and 5-HT2) were investigated in the cortex and hippocampus by radioligand binding studies using 3H-serotonin for analysis of 5-HT1-receptors and 3H-ketanserin for analysis of 5-HT2-receptors. Concentrations of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were significantly increased after hepatectomy compared with controls. Treatment with BCAA significantly decreased 5-HT and 5-HIAA levels in hepatectomized animals. The affinity and the number of binding sites for the 5-HT1 and 5-HT2 receptors were found to be similar in all groups. The present study indicates that PCS for 1 week and the anhepatic state for 5 hr in rats do not influence brain serotonin receptors in contrast to previous studies in pigs with liver ischemia or rabbits with galactosamine-induced liver damage. In addition, infusion of BCAA for 5 hr did not alter the binding characteristics.

The effect of liver ischaemia on brain monoamine synthesis in the rat.

SummarySubtotal or total liver ischaemia was induced in the rat by dividing the hepatic artery (Expt. I) or by total dearterialisation of the liver (Expt. II) 2 days after porta-caval shunt (PCS).The animals received i.v. a 10% glucose infusion for 5 h after the last operation and were killed by decapitation. At the end of the experiment all animals with liver ischaemia were in Grade III coma.In different regions of the CNS 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), were analysed by HPLC-technique with electrochemical detection, while dihydroxyphenylalanine (DOPA), dopamine (DA) and norepinephrine (NE) were analysed with a radio enzymatic method after blocking the decarboxylation of 5-HTP to 5-HT and DOPA to DA by inhibition of the aromatic amino acid decarboxylase enzyme with m-hydroxybenzylhydrazine (NSD 1015) in order to estimate the synthesis rate of 5-hydroxyindoles and catecholamines. In Expt. I concentrations of 5-HTP in animals with PCS were increased as compared to sham operation. In animals with liver ischaemia, 5-HTP concentrations were increased as compared to sham operation but similar to those in animals with PCS alone. These results suggest that ligation of the hepatic artery for 5 h in PCS animals does not further accelerate the rate of brain indole synthesis. In Expt. II, the 5-HTP concentrations were increased in PCS animals as compared to sham operation. Animals with total liver dearterialisation exhibited decreased 5-HTP levels as compared to PCS, suggesting a decreased brain indole synthesis after severe liver ischaemia.In Expt. II, CNS concentrations of DOPA following PCS were unaltered as compared with sham-operated animals. In animals with total liver dearterialisation, DOPA levels were increased, suggesting an augmented catecholamine synthesis. The NE levels were lower than in PCS and in shamoperated animals.

The effect of blood ingestion on brain serotonin synthesis in portacaval-shunted rats

SummaryIn rats with a portacaval shunt (PCS), the effect on the serotonin metabolism in the brain after oral administration of blood, a mixed amino acid solution (Vamin 14; KabiVitrum, Sweden) or a 10% glucose solution was studied. One week after PCS, the animals were fed with a gastric tube for 8 h and thereafter tested for behavioral abnormalities before decapitation at 12 h.The concentration of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were analyzed chromatographically (HPLC technique with electrochemical detection) in different regions of the brain. Estimation of synthetic rates of 5-hydroxyindoles was facilitated by aromatic aminoacid decarboxylase inhibition (m-hydroxybenzylhydrazine; NSD 1015).The brain concentrations of 5-HTP, 5-HT, and 5-HIAA were increased in all shunted rats as compared with sham-operated animals. Whether animals received blood, glucose, or aminoacid solution made no differences in the brain concentrations of 5-HTP and 5-HT. Concentrations of 5-HIAA were lower in those animals receiving blood as compared with the other shunted groups. No reproducible differences in the behavior of the animals were observed. These results suggest that massive blood administration 1 week after PCS in rats has no influence on the rate of brain indole synthesis. While alterations in serotonin metabolism may play a role in some forms of encephalopathy, this study implies that the behavioral and neurologic disorders which follow gastrointestinal tract hemorrhage in patients with liver failure may have other etiologies.

Amino Acids and Indoleamines in the Brain after Infusion of Branched-Chain Amino Acids to Rats with Liver Ischemia

Rats with a portacaval anastomosis and ligation of the hepatic artery 2 days later were infused for 6 hr with a 10% glucose solution (group I) or the same solution combined with 0.24 M/liter branched-chain amino acids (BCAA, group II). Control animals with portacaval anastomosis and sham-operation (group III) or two sham-operations (group IV) were infused with a 10% glucose solution. The rats were killed by decapitation and indoleamines and amino acids were determined in the brain. Rats with liver ischemia were stuporous at the end of the experiment irrespective of treatment. The concentrations in the cortex of lysine, methionine, phenylalanine, threonine, alanine, glutamine, glycine, histidine, and tyrosine were significantly increased in group I compared to group IV. Infusion of BCAA to rats with liver-ischemia (group II) resulted in significantly lower concentrations of lysine, methionine, phenylalanine, threonine, histidine and tyrosine and increased concentrations of isoleucine, leucine, valine, and arginine compared to group I. The content of serotonin in the cortex and brain stem was significantly increased in group I compared with the BCAA-treated animals (group II) and the control groups III and IV. The concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in the cortex and brain stem were higher in group I than in group IV. Infusion of BCAA to rats with liver ischemia normalized the concentrations of 5-HIAA in the cortex and brain stem.